Conclusion:- Prenatal diagnosis is now feasible from the moment of conception onward
. Imaging techniques have allowed non invasive diagnosis
while minimally invasive techniques concentrate on sampling maternal
blood for fetal cells or markers of feto placental metabolism.
Invasive techniques
have been rapidly expanding and becoming safer comprising
of A) chorionic villus
sampling B) early amniocentesis or C)
midtrimester amniocentesis as well as very early fetoscopy
and umbilical vein sampling Advances in prenatal diagnostic
techniques allow for earlier more rapid and more effective detection of congenital disorders
Recent advances in non invasive detection
methods such as fetal
ultrasound and the
isolation of fetal cells in the
maternal circulation allow the
intrauterine diagnosis of congenital infections and chromosomal and Mendelian disorders as well as
hematologic disorders.
We currently have the potential to diagnose a number of others for which the
opportunity has not yet arisen. If a A) biochemical B) morphologic C) chromosomal or D) genetic:-deoxyribonucleic
acid alternation is known for a specific condition and is likely to be expressed in one of the
fetal tissues or secretions attempt at prenatal diagnosis is reasonable .
Forget
CS /Lap ports!!!! Know what are gene probes???? Development of specific
gene probes
::Diagnosis of inherited disorders
in utero :-- Our ability to
detect the inherited disorders
in utero will continue to
improve both in the number of specific
disorders successfully diagnosed
or excluded and in the increasingly
earlier stages of pregnancy
at which the disorder can be
detected. Non invasive prenatal testing
and non invasive approach
involves analysis of cell
free fetal DNA in maternal
plasma or serum . Another approach
utilizes fetal cells within
the maternal circulation as a source
of fetal DNA.
Advances in instrumentation
have decreased the risk of the
invasive methods of prenatal
diagnosis and improvement in non invasive methods such as maternal serum screening may eliminate the need for invasive procedures altogether
.
Detection
of useful DNA polymorphisms linked to genes for specific diseases and development of specific
gene probes
have improved the accuracy
of diagnosis and reduced the need
for specific fetal tissues.
The entire genome of an individual is present
in each cell even though a specific
gene product may not be expressed
in that cell. Thus DNA
restriction endonuclease
studies can be performed
on amniotic fluid cells chorionic villi fetal cells in maternal circulation and fetal
tissues with equal facility.
The usefulness of prenatal diagnosis
will always be limited by the ability to detect
pregnancies at risk. If carrier
detection is unavailable the only way
to identify couples at risk
for offspring with an
autosomal recessive condition
is by the birth of an
affected child. For autosomal dominant and X linked recessive
and dominant conditions new mutations will continue to occur. As mentioned previously screening
of all pregnancies for all
defects is not possible now and is unlikely ever to be feasible either economically or technically . The reliability of prenatal diagnosis
will continue to depend upon accurate
diagnosis in the index case and upon the availability of a specific and sensitive test with no overlap in values between
heterozygotes and homozygotes for autosomal
recessive conditions or between
normal and affected fetuses with
autosomal dominant and X linked recessive
disorders . Correct
interpretation of test results is subject to experience recognition of artifact
and variation in the expression
of a given disorder in utero.
Prenatal diagnosis
of aneuploidy and single gene
disorders is usually performed by
collecting fetal samples through amniocentesis or CVS. However these invasive procedures
are associated with some
degree of risk to the fetus and or mother.
Forget about
Modern times”( Modern
Times is a 1936 American comedy film written and
directed by Charlie Chaplin in which his iconic Little Tramp character
struggles to survive in the ).Better think of more modern times written by, played by & directed by Dr Srimanta Pal “ . What is happening in MORE recent times? “.Therefore in recent years considerable
effort has been made to develop non invasive
prenatal testing and non invasive approach involves
analysis of cell free fetal
DNA in maternal plasma
or serum . Another approach utilizes fetal cells within the maternal circulation as a source
of fetal DNA .
In fact
cells and cffDNA can be
found circulating in maternal
blood .Fetal cells
recovered from maternal blood provide
the only source of pure fetal
DNA for NIPT. Fetal nucleated
erythrocytes are considered the most suitable maternally circulating fetal
cells for this purpose,
because they are not commonly found in the peripheral blood fo
healthy adult and are most
abundant in the fetus during early gestation . Because fetal cells
in maternal blood are
extremely rare a definitive separation
method has not yet been established. Fetal nucleated
erythrocytes can be enriched from maternal blood via fluorescednce or magnetic activated cell
sorting density gradients immune magnetic beads or micromanipulation. Fetal cells are identified ny Giemsa staining hybridization with Y chromosome specific probes
polymerase chain reaction detection of a specific paternal
allele or immune staining for
fetal cell antigens. Amplification
of fetal DNA sequences by primer extension
pre amplification and PCR has
allowed prenatal screening
for Duchenne muscular dystrophy
and the fetal Rhesus
blood type Sequence specific hybridization
has been used to detect
sickle cell anemia and beta thalassemia prenatally in heterozygous carriers
of these disorders Thus at the present time fetal
gender and fetal RgD
blood type within RhD negative
pregnant women can be
reliably determined through
analysis of maternal plasma. Furthermore genetic alterations can be
diagnosed in the maternal plasma when the mother does
not have the alterations. However
the diagnosis of maternally inherited genetic disease and aneuploidy is limited
using this approach . The use of
cffDNA in maternal plasma for the diagnosis of single gene disorders
is limited to disorders caused
by a paternally inherited gene or
a mutation that can be distinguished from the maternally inherited
counterpart . At present fetal gender
can be determined from maternal
plasma. When a pregnant
woman is a heterozygous carrier
of an X linked disorder the
determination of fetal gender is
clinically very informative for first
step screening to avoid invasive amniocentesis
. noninvasive prenatal diagnosis
of genetic disorders should be
applied to pregnant women with a definite
risk for a specific single gene disorder . Non invasive prenatal diagnosis through examination of intact fetal cells circulating within maternal blood can be used to diagnose a full range of genetic disorders . Since only a limited number of fetal cells circulate within maternal blood the above cited
procedures to enrich the cells and
enable single cell analysis with high sensitivity are required. Recently separation
methods including a lectin based
method and autoimage analyzing have been
developed which have improved the sensitivity of genetic analysis. This progress has supported the possibility of NIPD of genetic disorders .
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